Metabolism and genotoxicity of carcinogenic phenylpropanoids naturally occuring in food

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Phenylpropanoids are naturally occurring plant constituents. Some of them, e.g. safrole and methyleugenol have already been classified as genotoxic carcinogens. Little is known so far about the mechanism of carcinogenicity of alpha-, beta-, und gamma-asarone, which are found in essential oils of Acorus calamus und A. gramineus. The crucial mechanism of formation of an ultimate allylic carcinogenic metabolite described for safrole and others, is not transferable to alpha- and beta-asarone, due to the lack of an allylic side chain. Because of the limited metabolism data for asarone isomers and the lack of data on genotoxicity and mutagenicity of asarone metabolites, no mechanistic classification of the toxic profile of the parent compounds could been implemented so far. The Committee of Experts on Flavouring Substances of the Council of Europe evaluated beta-asarone in 2005 and pointed out the need for further studies on the mechanism of action of (beta-)-asarone carcinogenicity in particular for studies addressing the question whether beta-asarone is genotoxic or not. The aim of this research project is to investigate the metabolism of the three asarone isomers in experimental in vitro models from different species including humans . These will be used to investigate and characterize the genotoxic and mutagenic properties of asarones and their metabolites in order to assess their contribution to the toxicity and carcinogenicity of the parent compounds.